Erythroid cell adhesion molecules Lutheran and LW in health and disease

The Lutheran and LW glycoproteins are blood group-active proteins found at the surface of human red cells. The Lutheran glycoprotein (Lu gp) is a memb er of the immunoglobulin superfamily (IgSF) that binds the extracellular ma trix protein laminin, in particular, laminin isoforms containing the alpha 5 subunit. The LW glycoprotein (LW gp), also an IgSF member, has substantia l sequence homology with the family of intercellular adhesion molecules (IC AMs). LW gp binds the integrin very late antigen-4 (VLA-4, alpha(4)beta(1)) and alpha(v)-containing integrins. Studies on the expression of LW and Lu gps during erythropoiesis utilizing in vitro cultures of haemopoietic proge nitor cells have shown that LW gp expression precedes that of Lu gp. These observations have led to the suggestion that LW gp on erythroblasts may int eract with VLA-4 on macrophages to stabilize erythroblastic islands in norm al bone marrow and that Lu gp may facilitate trafficking of more mature ery throid cells to the sinusoidal endothelium where alpha 5-containing laminin s are known to be expressed. Levels of Lu gp and LW gp expression on sickle red cells are greater than on normal red cells and sickle red cells adhere to alpha 5-containing laminins. These data suggest that the Lu and LW mole cules may contribute to the vaso-occlusive events associated with episodes of acute pain in sickle cell disease.